Toxicological assessment of polychlorinated biphenyls and their metabolites in the liver of Baikal seal (Pusa sibirica).

We have previously reported that high accumulation of dioxins and related compounds induced cytochrome P450 (CYP 1s) isozymes in the liver of wild Baikal seals, implying the enhanced hydroxylation of polychlorinated biphenyls (PCBs). The present study attempted to elucidate the residue concentrations and patterns of PCBs and hydroxylated PCBs (OH-PCBs) in the livers of Baikal seals. The hepatic residue concentrations were used to assess the potential effects of PCBs and OH-PCBs in combination with the analyses of serum thyroid hormones, hepatic mRNA levels, and biochemical markers. The hepatic expression levels of CYP1 genes were positively correlated with the concentration of each OH-PCB congener. This suggests chronic induction of these CYP1 isozymes by exposure to PCBs and hydroxylation of PCBs induced by CYP 1s. Hepatic mRNA expression monitoring using a custom microarray showed that chronic exposure to PCBs and their metabolites alters the gene expression levels related to oxidative stress, iron ion homeostasis, and inflammatory responses. In addition, the concentrations of OH-PCBs were negatively correlated with L-thyroxine (T4) levels and the ratios of 3,3',5-triiodo-L-thyronine (T3)/reverse 3,3',5'-triiodo-L-thyroninee (rT3). These observations imply that Baikal seals contaminated with high levels of OH-PCBs may undergo the disruption of mechanisms related to the formation (or metabolism) of T3 and T4 in the liver.

A probabilistic model for the carry-over of PCDD/Fs from feed to growing pigs.

When food producing animals are contaminated with PCDD/F congeners, information on the contaminant's concentration in the bodies of the animals at time of slaughter is needed for risk management purposes. We have developed a mathematical model for the kinetics of PCDD/Fs in growing pigs in case of contaminated feed fed for a limited duration of time. This model allows the prediction of concentrations in body fat. It considers absorption fractions of PCDD/Fs, clearance by metabolism, dilution by growth and excretion through fecal fat. The model parameters were calibrated by fitting the model to experimental data. On the basis of this toxicokinetic model a probabilistic model has been constructed. The probabilistic model handles the parameters with appropriate probability distributions and Monte-Carlo simulation technique, providing for realistic situations with many animals and a range of contaminations and feeding intervals. We applied the new model to describe the German dioxin incident of winter 2010/2011 and discuss its viability as decision tool. The approach demonstrated here is a showcase how a risk assessment in the case of contaminated feeding can be performed.

Assessment of risk of PCDD/Fs and dioxin-like PCBs in marine and freshwater fish in Pearl River Delta, China.

Fish consumption is known to be beneficial to human health. However since the age of industrialization, the released/disposed chemical pollutants into water systems make fish a source of various environmental toxicants to humans. In oceanic cities with heavy industrial activities, fish products contribute the greatest proportion of exposure to pollutants. In this study, risks and potential effects of dioxins to health of coastal populations in the Pearl River Delta were assessed. Concentrations of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and dioxin-like polychlorinated biphenyls (PCBs) were measured in common fish species purchased at local markets. Concentrations of total dioxins in fish ranged from 0.481 to 9.05 pg TEQ/g wet weight were similar to the lesser concentrations reported for fish from other countries. The greatest concentrations of dioxins were measured in mandarin fish, a carnivorous freshwater fish. Exposure of murine primary leydig and ovarian cells to 2,3,7,8-tetrachlorinated dibenzo-p-dioxins (2,3,7,8-TCDD) reduced the synthesis of progesterone, testosterone and/or estrogen. The reductions were probably via inhibitory effects on the expression of the steroidogenic enzymes, steroidogenic acute regulatory protein (StAR) and cytochrome P450 side-chain cleavage enzyme (P450scc). Based on these reproductive parameters, the concentrations of dioxins and dioxin-like residues represent a moderate health risk due to consumption of fish.

Exposure assessment of dioxins and dioxin-like PCBs in pasteurised bovine milk using probabilistic modelling.

Quantitative exposure assessment is a useful technique to investigate the risk from contaminants in the food chain. The objective of this study was to develop a probabilistic exposure assessment model for dioxins (PCDD/Fs) and dioxin-like PCBs (DL-PCBs) in pasteurised bovine milk. Mean dioxins and DL-PCBs (non-ortho and mono-ortho PCBs) concentrations (pg WHO-TEQ g(-1)) in bovine milk were estimated as 0.06 ± 0.07 pg WHO-TEQ g(-1) for dioxins and 0.08 ± 0.07 pg WHO-TEQ g(-1) for DL-PCBs using Monte Carlo simulation. The simulated model estimated mean exposure for dioxins was 0.19 ± 0.29 pg WHO-TEQ kg(-1)bw d(-1) and 0.14 ± 0.22 pg WHO-TEQ kg(-1) bw d(-1) and for DL-PCBs was 0.25 ± 0.30 pg WHO-TEQ kg(-1) bw d(-1) and 0.19 ± 0.22 pg WHO-TEQ kg(-1) bw d(-1) for men and women, respectively. This study showed that the mean dioxins and DL-PCBs exposure from consumption of pasteurised bovine milk is below the provisional maximum tolerable monthly intake of 70 pg TEQ kg(-1) bw month(-1) (equivalent of 2.3 pg TEQ kg(-1) bw d(-1)) recommended by the Joint FAO/WHO Expert Committee on Food Additives and Contaminants (JECFA). Results from this study also showed that the estimated dioxins and DL-PCBs concentration in pasteurised bovine milk is comparable to those reported in previous studies.

Risk assessment of PCDD/Fs levels in human tissues related to major food items based on chemical analyses and micro-EROD assay.

Nine groups of food items (freshwater fish, marine fish, pork, chicken, chicken eggs, leafy, non-leafy vegetables, rice and flour) and three types of human samples (human milk, maternal serum and cord serum) were collected for the analysis of PCDD/Fs. Results of chemical analysis revealed PCDD/Fs concentrations (pg g(-1) fat) in the following ascending order: pork (0.289 pg g(-1) fat), grass carp (Ctenopharyngodon idellus) (freshwater fish) (0.407), golden thread (Nemipterus virgatus) (marine fish) (0.511), chicken (0.529), mandarin fish (Siniperca kneri) (marine fish) (0.535), chicken egg (0.552), and snubnose pompano (Trachinotus blochii) (marine fish) (1.219). The results of micro-EROD assay showed relatively higher PCDD/Fs levels in fish (2.65 pg g(-1) fat) when compared with pork (0.47), eggs (0.33), chicken (0.13), flour (0.07), vegetables (0.05 pg g(-1) wet wt) and rice (0.05). The estimated average daily intake of PCDD/Fs of 3.51 pg EROD-TEQ/kg bw/day was within the range of WHO Tolerable Daily Intake (1-4 pg WHO-TEQ/kg bw/day) and was higher than the Provisional Tolerable Daily Intake (PMTL) (70 pg for dioxins and dioxin-like PCBs) recommended by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) [Joint FAO/WHO Expert Committee on Food Additives (JECFA), Summary and conclusions of the fifty-seventh meeting, JECFA, 2001.]. Nevertheless, the current findings were significantly lower than the TDI (14 pg WHO-TEQ/kg/bw/day) recommended by the Scientific Committee on Food of the Europe Commission [European Scientific Committee on Food (EU SCF), Opinions on the SCF on the risk assessment of dioxins and dioxin-like PCBs in food, 2000.]. However, it should be noted that micro-EROD assay overestimates the PCDD/Fs levels by 2 to 7 folds which may also amplify the PCDD/Fs levels accordingly. Although the levels of PCDD/Fs obtained from micro-EROD assay were much higher than those obtained by chemical analysis by 2 to 7 folds, it provides a cost-effective and rapid screening of dioxin levels in food and human samples.

Bioanalytical characterization of dioxin-like activity in sewage sludge from Beijing, China.

In this preliminary study, the bioanalytical characterization of dioxin-like activity in the sludge of all the nine municipal sewage treatment plants from Beijing city was studied using chemically activated luciferase gene expression (CALUX) assay. The influence of heating period in winter, sewage and sludge treatment processes on the occurrence of dioxin-like activity was also discussed. For the use of clean coal and natural gas, heating did not have significant influence on the occurrence level of PCDD/Fs and dioxin-like-PCBs in this study. Anaerobic-aerobic-anoxic sewage treatment process did not show a good performance in the reduction of dioxin-like activity which is useful in the removal of chemical oxygen demand (COD) and nitrogen. Anaerobic digestion of sludge increased the concentration of PCDD/Fs from 30.1 to 68.3pgCALUX-TEQg(-1)d.w., and total dioxin-like activity from 32.2 to 69.3pgCALUX-TEQg(-1)d.w. This cost-effective and quick test is useful for large developing countries like China in monitoring programs to obtain baseline data about the scale of contamination caused by dioxin-like activity. It is also a useful component in the monitoring capacity building of dioxins.

Preliminary health risk assessment for polybrominated diphenyl ethers and polybrominated dibenzo-p-dioxins/furans in seafood from Guangzhou and Zhoushan, China.

Dietary intake is one of the important routes of human exposure to brominated flame retardants (BFRs) such as polybrominated diphenyl ethers (PBDEs). The use of PBDEs may also result in exposure to polybrominated dibenzo-p-dioxins and dibenzofurans (PBDDs/DFs), as these compounds are impurities in technical mixtures of BFRs and can also be formed unintentionally by the same processes that generate chlorinated dioxins. This study determined the concentrations of polybrominated compounds in common seafood in Guangzhou and Zhoushan, and assessed the health risks of these chemicals via consumption of contaminated seafood. Seafood samples (fish, bivalves, shrimp, crab, and cephalopods) purchased from local markets in 2003 and 2004 were analyzed for PBDEs and PBDDs/DFs. The highest concentration of total PBDEs (46.3 ng g(-1) lipid wt.) was detected in fish from Guangzhou, in which BDEs 47 and 209 were the two predominant congeners. The total daily intakes of PBDEs, PBDDs, and PBDFs were, 946, 6.39, and 6.54 pg kg(-1) body weight (bw) in Guangzhou, and 489, 4.99, and 7.65 pg kg(-1) bw in Zhoushan, respectively. The hazard ratios for PBDDs and PBDFs were both greater than unity, indicating that these compounds may pose some health risks to the local population.

Human dietary intake of organochlorines from Baltic herring: implications of individual fish variability and fisheries management.

This study examines the extent to which Finnish human dietary intake of organochlorines (PCDD/Fs and PCBs) originating from Northern Baltic herring can be influenced by fisheries management. This was investigated by estimation of human intake using versatile modeling tools (e.g., a herring population model and a bioenergetics model). We used a probabilistic approach to account for the variation in human intake of organochlorines originating from the variation among herring individuals. Our estimates were compared with present precautionary limits and recommendation for use. The results show that present consumption levels and frequencies of herring give a high probability of exceeding recommended intake limits of PCDD/Fs and PCBs. Furthermore, our results clearly demonstrate that in the risk management of dioxinlike organochlorines, regulating fishing (in this case increasing fishing pressure) is a far less effective way to decrease the risk than regulating the consumption of herring. Increased fishing would only slightly decrease organochlorine concentrations of herring in the Finnish fish market.

Uptake of dioxin-like compounds from sewage sludge into various plant species--assessment of levels using a sensitive bioassay.

A bioassay for the detection of dioxin-like compounds was used to estimate uptake of dioxin-like compounds in carrots, oil seed rape seeds, zucchinis and cucumbers grown in soil amended with sewage sludge from Swedish sewage treatment plants (STP). This sensitive bioassay is based on 7-ethoxyresorufin O-deethylase (EROD)-induction in cultured chicken embryo livers and reflects the combined biological effect of all dioxin-like compounds in a sample, including ones that seldom are analyzed. The bioassay detected low concentrations of dioxin-like compounds in all carrot, zucchini and cucumber samples, but did not detect any dioxin-like compounds in the rape seeds. In carrots the concentrations were increased up to seven times when grown in soil amended with high applications of some of the sludge samples, while others did not increase the concentrations compared to control. More realistic sludge applications only increased the concentrations slightly. The sludge-fertilized carrots contained the highest concentrations of the investigated plants (up to 14 pg bioassay-derived TCDD equivalents (bio-TEQs)/g d.w.). In the carrots, differences in uptake of dioxin-like compounds depended on the sludge origin, which may be due to more easily bioaccumulated dioxin-like compounds in some sludge samples, or other components that facilitated uptake into the carrots. In the cucumbers, a more than two-fold increase (from 0.2 to 0.5 pg bio-TEQs/g d.w.) was observed in specimens grown in sludge-amended soil when compared to controls, suggesting a small uptake from the roots to the shoots. No sludge-dependent increase in uptake was seen in the zucchini fruits. The bio-TEQ levels were generally low in the consumable above ground plant parts of the investigated species. However, the question if repeated sludge application results in a soil accumulation of dioxin-like compounds, thereby increasing the risk of plant uptake, remains to be investigated.

Toxicity of dioxins: role of an absolute hardness-absolute electronegativity diagram (eta-chi diagram) as a new measure in risk assessment.

The differences in biological activities among polychlorinated dibenzo-p-dioxins (dioxins) are strongly dependent on the substitution pattern of chlorine at various positions on the parent dibenzo-p-dioxin molecule. The absolute hardness, eta, of dioxins shows a good correlation with the potency of biological activity and the chlorine substitution pattern. The result means that the soft dioxins have a small HOMO-LUMO gap, and are more toxic than the hard dioxins. Therefore, the values of absolute hardness, eta, of dioxins can be used to predict their toxic potency (dioxin hardness). Moreover, we show that the absolute hardness-absolute electronegativity (eta-chi) diagrams, as an activity coordinate, play an important role as a new measure in the assessment of the toxicity and potency of the biological activity of dioxins.

Dioxin bioaccumulation: key to a sound risk assessment methodology.

Human exposure to many pollutants occurs primarily through the ingestion of contaminated fish. In order to protect human health, regulatory agencies set limits on the levels of pollutants entering water bodies from point sources, thereby limiting the amount of pollutants that may be accumulated by fish. The limits, in the form of water quality criteria, are designed to correlate the concentration of a pollutant in a water body (and therefore the concentration accumulated by a fish) to the risks to humans. This type of model provides a reasonable way of controlling pollutants from point sources if the assumptions used in the model are realistic. However, the risk assessment formula currently used for developing water quality criteria only considers those pollutants in the water column available to fish through bioconcentration across the gills (freely dissolved pollutants). For strongly hydrophobic pollutants like dioxin, an extremely small fraction of the total amount is freely dissolved; most dioxin is sorbed to organic matter and is ingested by fish. A new model for developing criteria is presented here that takes into account the environmental fate of dioxin (predominantly in the sorbed state in the environment) and that fish accumulate dioxin by ingestion, rather than bioconcentration.

Human exposure to environmental polychlorinated dibenzo-p-dioxins and dibenzofurans: an exposure commitment assessment for 2,3,7,8-TCDD.

Polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDDs and PCDFs) are released into the environment from the use of chemicals contaminated with PCDDs/PCDFs, the improper disposal of contaminated production wastes and incineration/other high-temperature processes. Certain congeners are extremely stable compounds which are persistent in the environment once released. An assessment is made of the sources of human exposure to one particular dioxin congener, 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD). Representative values of 2,3,7,8-TCDD concentrations in the background environment and in man are selected from available data or, when not available, inferred from other relevant information. A pathway analysis is performed utilizing the exposure commitment method. Normal dietary intake of 2,3,7,8-TCDD is quite variable depending primarily on consumption of contaminated fish. Representative intake for the average adult of 0.1 ng day-1 may be associated with a human body burden of 100 ng (approximately 7 ng 2,3,7,8-TCDD kg-1 adipose tissue). The inferred biological half-time of this compound in the body is approximately 5 years. The exposure evaluation also accounts for secondary pathways to man of 2,3,7,8-TCDD in air and drinking water. Estimates of transfer factors obtained from the representative background levels should be generally relevant and may be applied to more specific cases of exposure.

Health hazard assessment for chlorinated dioxins and dibenzofurans other than 2, 3, 7, 8-TCDD.

EPA is faced with the need to perform health risk assessments of environmental materials containing mixtures of chlorinated dioxins and -dibenzofurans. Preferably, such an assessment must be based on the direct evaluation of chronic health effects of the mixture or on a knowledge of the toxic effects of each of the components. In the absence of such data, the authors have developed two pragmatic approaches that can reasonably be applied to mixtures such as flyash or contaminated soil. The details of these approaches, viewed as interim procedures, are compared and contrasted with those used by other regulatory and public health authorities.